The objective of this research is to investigate the membrane mechanisms that underlie the myotonic reaction, i.e., abnormal, prolonged, repetitive discharge of impulses, and abnormal contractions of skeletal muscle fibers. Electrophysiological and pharmacological methods will be used to continue studies of the skeletal muscle of normal and congenitally myotonic goats and of Rottnest Quokkas, and to compare the repetitive responses and other myotonia-related signs in the muscle of various species when these conditions are induced by chemical agents, denervation, ionic changes, hereditary disease, and other treatments. The voltage-clamp method will be used with the intention of better defining the ionic basis of myotonic behavior of these fibers. Experiments have been proposed to test the generality of the low-chloride conductance channel, and the involvement of the transverse tubular system (including voltage-dependent charge movement) in the myotonic response. The ultimate aims are to elucidate mechanisms of repetitive responsiveness and other related signs as they occur in myotonia congenita or elsewhere, and to relate this knowledge to excitation of normal muscle membranes, and the action of drugs or disease processes which alter these properties, thus making possible the control of these phenomena. BIBLIOGRAPHIC REFERENCES: Bryant, S.H. & Camerino, D.(1976). Chloride conductance of denervated gastrocnemius fibers from normal goats. J. Neurobiology 7: 229-240. Camerino, D., & Bryant, S.H. (1976). Effects of denervation and colchicine treatment on the chloride conductance of rat skeletal muscle fibers. J.Neurobiology 7: 221-228.